Official Title: “Diclofenac for the Prevention of Post-ERCP Pancreatitis in Higher Risk Patients: A Prospective, Randomized, Double Blind, Placebo Controlled Trial.”

Inflammation of the pancreas (pancreatitis) is an uncommon but potentially serious complication of endoscopic retrograde cholangiopancreatography (ERCP), a specialized endoscopic examination of the ducts draining the liver and pancreas. Although many different strategies have been tried and studied in attempts to reduce this risk, few have been shown to make a significant difference. Those that have are either very expensive, difficult to administer, or both. Diclofenac, an anti-inflammatory medication most often used to treat arthritis, has shown potential to decrease the risk of post-ERCP pancreatitis. It can be given after the procedure to patients at most risk for the complication, and has few side effects. This study will randomize people in the study to placebo or active medication, to determine if Diclofenac reduces the incidence of pancreatitis.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: October 2010

Hypothesis:

Diclofenac, when administered immediately post ERCP in patients at higher risk of developing post-ERCP pancreatitis, will significantly reduce the incidence of this complication.

Methods:

Inclusion Criteria:

These were chosen based on a review of the major studies evaluating risk factors for post-ERCP pancreatitis. Any of the following factors placing a patient at high risk (>10%) of post ERCP pancreatitis: - Patient characteristics: Prior history of post-ERCP pancreatitis, prior history of acute pancreatitis, suspected Sphincter of Oddi dysfunction, or normal bilirubin; - Procedure related factors: Moderate (6-15 attempts) and difficult (>15 attempts) bile duct cannulation, balloon dilation of the biliary sphincter, pre-cut papillotomy, pancreatic sphincterotomy.

Exclusion Criteria: - Ongoing acute or chronic pancreatitis; - Previous biliary sphincterotomy; - Contra-indications to non-steroidal anti-inflammatory medications (allergy, reduced renal function, recent upper gastrointestinal bleeding); - Ingestion of an NSAID in the previous 7 days.

Intervention:

All patients undergoing ERCP not having exclusion criteria will be approached for participation prior to the procedure. At the end of the procedure, prior to transfer from the endoscopy suite, within 15 minutes of the end of the procedure, if the patient meets inclusion criteria, a study suppository will be administered. The suppositories will be prepared by a study pharmacist according to a randomization list prepared by an independent biostatistician. They will be randomized using a permuted block design, in blocks of 20. The placebo is inert, and identical to the study medication, a 100 mg diclofenac rectal suppository. The code will not be broken until enrolment of patients is complete.

Patients, endoscopists, nurses, and the principal investigator will all be blinded to the randomization code.

Outcomes:

Post-ERCP acute pancreatitis is the primary outcome. Consensus definition of this is new typical (epigastric/retroperitoneal) pain combined with an elevation of serum lipase or amylase >3 times the upper limit of normal. Pain will be assessed through history and physical exam by an attending gastroenterologist the morning after the procedure, with documentation in the chart and research form of the presence or absence of pain. Serum amylase will be measured the morning after the procedure, between 7 and 10 am (approximately 18 hours post procedure). Most patients will be inpatients but outpatients will be included if they can be assessed through clinical exam and blood chemistry analysis the following morning. Patients will be contacted one week after the procedure to ensure no episode of abdominal pain or bleeding has been missed.

Statistics and Power Calculation

A two sided Fisher's Exact Test will be used to compare the proportion of patients developing post-ERCP pancreatitis in each group (placebo vs. active drug). In the population selected, the estimated risk of pancreatitis is 15%. To demonstrate a decrease to 5%, 141 patients will be required in each group, with 80% power and an alpha error 0.05. Secondary outcomes will include severity of pancreatitis, hyperamylasemia, length of stay, and mortality. Safety data regarding renal function and GI bleeding will also be collected.

Intervention(s) in this Clinical Trial

• Drug: diclofenac
  • 100 mg diclofenac rectal suppository
• Drug: placebo
  • similar shape and size suppository

Arms, Groups and Cohorts in this Clinical Trial

• Placebo Comparator: 1
  • placebo suppository
• Active Comparator: 2
  • diclofenac suppository

Primary Measures

• post-ercp pancreatitis
  • Time Frame: 24 hours
    Safety Issue?: Yes

Secondary Measures

• severity of pancreatitis, side effects
  • Time Frame: 30 days
    Safety Issue?: Yes

Inclusion Criteria:

• Any of the following factors placing a patient at high risk (>10%) of post ERCP pancreatitis:
• Patient characteristics: Prior history of post-ERCP pancreatitis, prior history of acute pancreatitis, suspected Sphincter of Oddi dysfunction, or normal bilirubin;
• Procedure related factors: Moderate (6-15 attempts) and difficult (>15 attempts) bile duct cannulation, balloon dilation of the biliary sphincter, pre-cut papillotomy, pancreatic sphincterotomy.

Exclusion Criteria:

• Ongoing acute or chronic pancreatitis;
• Previous biliary sphincterotomy;
• Contra-indications to non-steroidal anti-inflammatory medications (allergy, reduced renal function, recent upper gastrointestinal bleeding);
• Ingestion of an NSAID in the previous 7 days.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Queen's University

Overall Clinical Trial Officials and Contacts

Lawrence Hookey, MD Principal Investigator Queen's University  

Overall Contact: Lawrence Hookey, MD (613) 544-3400 hookeyl@hdh.kari.net

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00428025

Study ID Number: diclofenac trial hookey

ClinicalTrials.gov Identifier: NCT00428025

Health Authority: Canada: Health Canada